Pubmed du 28/06/21
1. Dell’ Amico C, Tata A, Pellegrino E, Onorati M, Conti L. Genome editing in stem cells for genetic neurodisorders. Progress in molecular biology and translational science. 2021; 182: 403-38.
The recent advent of genome editing techniques and their rapid improvement paved the way in establishing innovative human neurological disease models and in developing new therapeutic opportunities. Human pluripotent (both induced or naive) stem cells and neural stem cells represent versatile tools to be applied to multiple research needs and, together with genomic snip and fix tools, have recently made possible the creation of unique platforms to directly investigate several human neural affections. In this chapter, we will discuss genome engineering tools, and their recent improvements, applied to the stem cell field, focusing on how these two technologies may be pivotal instruments to deeply unravel molecular mechanisms underlying development and function, as well as disorders, of the human brain. We will review how these frontier technologies may be exploited to investigate or treat severe neurodevelopmental disorders, such as microcephaly, autism spectrum disorder, schizophrenia, as well as neurodegenerative conditions, including Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and spinal muscular atrophy.
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2. Lan J, Hu Y, Wang X, Zheng W, Liao A, Wang S, Li Y, Wang Y, Yang F, Chen D. Abnormal spatiotemporal expression pattern of progranulin and neurodevelopment impairment in VPA-induced ASD rat model. Neuropharmacology. 2021; 196: 108689.
Some environmental risk factors have been proven to contribute to the etiology of autism spectrum disorder (ASD). Exposure to the antiepileptic drug valproic acid (VPA) during pregnancy significantly increases the risk of ASD in humans, and consequently is utilized as a validated animal model of ASD in rodents; however, the precise molecular and cellular mechanisms remain ill-defined. In the present study, we investigated the effect of prenatal VPA exposure on the spatiotemporal dynamics of Progranulin (PGRN) expression, neuronal apoptosis, synapse density, and AKT/GSK-3β pathway activation in the brains of VPA-exposed offspring. Results from behavioral tests were consistent with prior studies showing impaired sociability, restricted interests and increased repetitive behaviors in VPA rats at postnatal days 28-32. Our data also indicated that VPA exposure resulted in abnormal dynamics of PGRN expression in different brain regions at the different development stages. The temporal and spatial patterns of PGRN expression were consistent with the spatiotemporal regularity of abnormalities, which observed in apoptosis-related protein levels, neuron numbers, dendritic spine density, synapse-related protein levels, and AKT/GSK-3β phosphorylation in VPA rats. It suggests that prenatal VPA exposure may affect the spatiotemporal regularity of neuronal apoptosis and synaptic development/regression via interfering with the spatiotemporal process of PGRN expression and downstream AKT/GSK-3β pathway activation. This may be a potential mechanism of the abnormal neuroanatomical changes and ASD-like behaviors in VPA-induced ASD.
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3. McQuoid J, Thrul J, Lopez-Paguyo K, Ling PM. Exploring multiple drug use by integrating mobile health and qualitative mapping methods – An individual case study. The International journal on drug policy. 2021; 97: 103325.
BACKGROUND: Multiple drug use involves particular pleasures and risks, and is disproportionately practiced by some minority and socially marginalized groups. The unique patterns, intentions, and social contexts of multiple drug use for these groups are poorly understood. METHODS: Our mixed method integrates geo-enabled smartphone survey data collection with a qualitative mapping interview method. This brief report presents data from one study participant to demonstrate this method’s potential contributions to multiple drug use research for priority groups in different settings. RESULTS: ‘Jason’s’ data revealed the interrelated dynamics within his drug use repertoire and links between his substance use to rural life as a transgender person with autism spectrum disorder (ASD). Cigarettes played a role in coping with acute stress from repeatedly being misgendered. Cannabis intoxication helped manage social interactions as a person with ASD, while ‘chasing’ with cigarettes calibrated cannabis intoxication. Methamphetamine use related to managing body dysmorphia in a rural context with poor access to transgender health services. CONCLUSION: This mixed method can integrate reliable and ecologically valid assessments of multiple drug use repertoires and combination patterns with the place-embedded experiences, intersecting identities, structural barriers, and intentions related to multiple drug use for different priority groups.
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4. Poulin CJ, Fox AE. Preliminary evidence for timing abnormalities in the CNTNAP2 knockout rat. Behavioural processes. 2021; 190: 104449.
The CNTNAP2 gene has been implicated in several neuropsychological disorders, including autism spectrum disorder (ASD) and schizophrenia. The CNTNAP2 knockout (KO) rat model, rats without the CNTNAP2 gene, exhibits deficits in social interaction and increases in both repetitive and anxiety-like behaviors. However, deficits in time perception that may underlie several of the neuropsychological disorders implicated have not been investigated. The current study investigated timing in CNTNAP2 KO rats compared to control rats using a discrete-trial temporal bisection task. Results suggested deficits in the timing of relatively long durations in the CNTNAP2 KO rats. This finding is consistent with similar findings previously reported in humans diagnosed with ASD, and is promising for understanding the role that the CNTNAP2 gene may play in timing in certain neuropsychological disorders, and for developing targeted clinical therapies.
